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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5238_Библиотеки_им_академика_М_И_Перельмана.pdf
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A.-L. Sutter-Dallay and F. Gressier
rate of gestational diabetes (2.09 [1.21–3.70]) compared with controls (non-BD and
not exposed to mood stabilizers during pregnancy).
A preventive and multidisciplinary approach is therefore essential for women
with BD.If pregnancy is not yet planned, contraceptive methods should be discussed with the patient, as certain anticonvulsant mood stabilizers are potent enzyme
inducers that reduce the efcacy of oral contraceptives or progestogen-releasing
implants (e.g., carbamazepine, oxcarbazepine and topiramate) (Ernst and Goldberg
2002). Conversely, ethinyl oestradiol/levonorgestrel combined oral contraceptives
increase lamotrigine clearance (Clark et al. 2013; Gafeld etal. 2011). Women
should also be informed about the effects of these treatments on their fertility, particularly regarding valproate, which is likely to be associated with increased testosterone levels and hyperandrogenism in women with BD (Zhang etal. 2016). In
addition, women should be informed about the risk of unintended pregnancy when
discontinuing hyperprolactinemia-inducing antipsychotics used as mood stabilizers. As far as pregnancy is concerned, the specicities of managing BD in the perinatal period can be addressed in the context of gynaecological and/or psychiatric
care, and well before pregnancy in the case of a pre-existing diagnosis. Indeed, the
ethical dimension of weighing up the benets and risks of each pregnancy is crucial
and must take into account the risk of relapse, the potential effects of mood stabilizers on embryonic and foetal development, and the wishes of the woman and the
couple, which is a time-consuming issue for parents. Faced with a planned or ongoing pregnancy on mood stabilizers, the patient and her partner must be supported
throughout the risk-benet analysis, based on a multiprofessional approach combining psychiatric, obstetric, and paediatric knowledge for each molecule, taking into
account the specic evolutionary features of each patient’s disorder and her wishes.
Data on mood stabilizers in pregnancy are still relatively scarce, although they
are increasing rapidly. Unfortunately, most studies do not take into account the
inuence of maternal somatic disorders on foetal development and pregnancy, such
as malnutrition, obesity, diabetes, gynaecological infections, or the inuence of
environmental factors such as unhealthy lifestyles or domestic violence. Bearing
these general limitations in mind, a summary of the current literature allows a general prescriptive framework to be dened.
Table 10.1 presents expert recommendations based on scientic evidence and
clinical experience on the use of mood stabilizers during pregnancy.
10.2 Lithium
10.2.1 Placental Transfer
The rst works of Newport etal. (2005) about placental transfer of lithium combined the results of a prospective sample of 10 women with 32 cases of neonatal
dosages identied in the literature and suggested that placental transfer of lithium
was complete and that the balance between maternal and foetal circulation (average
child/mother plasma lithium ratio =1.05 ratio) is as between the different uid
10 Mood Stabilizers inPregnancy
263
Table 10.1
Regarding the increased risk of bipolar disorder episodes during pregnancy clinicians have to
be able to prescribe after weighing the risks of a maternal relapse vs. the risks of antenatal
exposure to the drug
To date the available limited data suggest that there is no contraindication regarding the use of
lamotrigine
The available limited data suggest that there is no longer absolute contraindication regarding
the use of lithium during the rst trimester of pregnancy
Valproate must be avoided because of the increased risk of defects and developmental
disorders for the child
Carbamazepine may increase birth defects, and impact some developmental axes
Bipolar women must be treated during pregnancy, to avoid risk-taking behavior and
deterioration in the prognosis of the disorder over the long term as well as the risks for the
fetus of the effects of prenatal stress, increased smoking or poor nutritional intake
Expert recommendations based on scientic evidence and clinical experience
compartments of an individual. Another study (van der Lugt etal. 2012) found neonatal blood lithium levels above 0.8mEq/l in 2 of the 30 exposed children, one of
which presented signs of neonatal distress. A recent retrospective observational
cohort study (Imaz etal. 2024) including 66 women with BD and stable with lithium in late pregnancy for whom it was discontinued 12h before a scheduled caesarean section or induction, or at admission day to hospital birth and restarted
6–12hours post birth, found a mean (SD) umbilical cord/mother intrapartum lithemia ratio of 1.10 (0.17), mean lithemia were 0.178mEq/L higher in infant with
hypotonia than in those without (p=0.028). However, there was an early postpartum relapse for 6% of the mothers.
Finaly, the recent paper by Molenaar etal. (2024) on 233 maternal lithium blood
level measurements—55 (23.6%) in the week before delivery and 178 (76.4%) in
the week after—found no association between time and lithium blood level/dose
ratio (Pearson correlation coefcient−0.03, P=0.63). In addition, 29 neonates
who had a lithium measurement within 24h of birth showed that maternal and neonatal lithium blood levels were strongly correlated and that there was no association
between neonatal lithium blood levels at birth and neonatal outcomes. Based on
these ndings, authors do not recommend lowering the dosage or discontinuation of
lithium prior to delivery, as stable dosing can prevent subtherapeutic lithium serum
levels, which is especially important in the postpartum period when relapse risks are
highest.
Note that the co-prescription of other psychotropic drugs is not taken into account
in any of these studies.
10.2.2 Embryonic Period: Organogenesis
The rst studies on lithium teratogenicity are animal studies dating from the end of
the nineteenth century. In animals exposed antenatally to doses used for treatment
in human beings, no increase in teratogenic risk has been noticed. With very high
doses, some studies reveal different types of malformations (central nervous
264
A.-L. Sutter-Dallay and F. Gressier
system, skeletal, craniofacial...), while others did not nd any link between prenatal
exposure to lithium and birth defects (Giles and Bannigan 2006). The rst data on
lithium’s teratogenicity in humans are issued from the “Register of Lithium Babies
“, which collected retrospectively the pregnancy outcomes of patients treated by
lithium in Scandinavia, the United States, and Canada. The rst publication reported
118 cases of Scandinavian children whose mothers had taken lithium during the rst
trimester of pregnancy (Schou etal. 1973). Nine of them (7.6%) presented birth
defects, among which 6 were related to the cardiovascular system, including 1
Ebstein anomaly (severe malformation of the tricuspid valve). By adding other data
from the United States and Canada, the number of cases reported increased to 143.
In this second sample, cardiovascular malformations accounted for 77% of congenital defects, against 12.5% in the general population. Ebstein’s anomaly was largely
over-represented with 40% of the babies from the registry presenting with this
pathology against 1.25% in the general population. The nal publication (Weinstein
and Goldeld 1975) included 225 observations (with at least 3 children who were
also exposed to other treatments), among which 11% (n=25) of the children presented congenital malformations (against 2% in the general population). Threequarters of these malformations were cardiovascular (n=18) and 33% (n=6) were
Ebstein anomalies. The retrospective collection of data in this register represents a
major bias, since it is likely that pathological cases have been more frequently
reported than normal births. Subsequent retrospective studies used more strict data
collection methods, and did not reveal statistically signicant relation between the
use of lithium during pregnancy and the occurrence of cardiac malformations in the
newborn, nor specic links between Ebstein’s anomaly and prenatal exposure to
lithium (Nora etal. 1974; Kozma 2005). For example, the review of 59 cases of
Ebstein diseases found no cases of children exposed to lithium in early pregnancy
(Zalzstein etal. 1990).
Thereafter, the study by Patorno etal. (2017), which showed an adjusted risk
ratio of cardiac malformations in lithium-exposed infants compared with unexposed
infants of 1.65, highlights also that the risk ratio was 1.11 for a daily dose of 600mg
or less, 1.60 for 601 to 900mg, and 3.22 for more than 900mg, suggesting a doseresponse relationship.
Prospective studies remain rare to date and mainly do not show a statistically
signicant link with birth defects, although some note the existence of sporadic
cases of Ebstein’s anomaly. For example, the prospective, comparative observational study of Diav-Citrin etal. (2014) followed up 183 lithium-exposed pregnancies of women who contacted the Israeli Teratology Information Service (90.2% in
the rst trimester) and were compared with 72 disease-matched and 748 nonteratogenic-exposed pregnancies. The rate of major congenital anomalies was not signicantly different between the groups (lithium-exposed in the rst trimester: 8/123
[6.5%]; bipolar: 2/61 [3.3%]; nonteratogenic: 19/711 [2.7%]). Cardiovascular
anomalies occurred more frequently in the lithium group exposed during the rst
trimester when compared with the nonteratogenic exposure group (5/123 [4.1%]
compared with 4/711 [0.6%]) but not after excluding anomalies that spontaneously
resolved (3/123 [2.4%] compared with 2/711 [0.3%]).
10 Mood Stabilizers inPregnancy
265
Case-control studies have failed to demonstrate a signicant association between
birth defects and in utero exposure to lithium (Zalzstein etal. 1990; Gentile 2012)
when case reports in the literature indicate both heart defects, sometimes with
Ebstein’s anomaly, other types of defects, including neural tube defects
(Gentile 2012).
Finally, a meta-analysis (McKnight etal. 2012) about general toxicity of lithium
concluded that the risk of congenital malformation after early in-utero exposure to
lithium is “uncertain”, and that the benet-risk balance of a decrease or a discontinuation of treatment during pregnancy should be weighed for each clinical situation. Facing a probably slight increased risk of heart defects in this population, it is
therefore recommended that all women receiving lithium during pregnancy should
undergo fetal echocardiography and a level-2 (anatomic scan) ultrasound examination between 18 and 20weeks of gestation (Bergink and Kushner 2014).
A recent systematic review and network meta-analysis of congenital malformations and prenatal outcomes exploring the comparative safety of antipsychotic medications and mood stabilizers during pregnancy in 18,334 potential records, and 22
studies, involving 3,042,997 pregnant women, found that, compared with the unexposed group, lithium (OR, 1.61; 95% credible interval (CrI) 1.07–2.30), risperidone
(OR, 1.43; 95% CrI 1.18–1.77), olanzapine (OR, 1.33; 95% CrI 1.11–1.64), aripiprazole (OR, 1.30; 95% CrI 1.10–1.65), and quetiapine [odds ratio (OR), 1.19; 95%
CrI, 1.01–1.39] were associated with a slightly increased risk of congenital
malformations.
From a cardiological perspective, a recent meta-analysis of risk factors for congenital heart disease (CHDs) (Lemieux etal. 2024) compiling 131 articles, associations between antenatal exposure to psychotropic drugs and CHDs a positive
association was observed between severe CHDs and lithium, but with a very wide
CI encompassing the null effect (OR of 3.11 (95% CI, 0.32–30.22) and with high
heterogeneity (I2= 54.3%)), when the association with maternal antidepressants
exposure was stronger (OR, 1.23; 95% CI, 1.09–1.38).
Boyle etal. (2017), in a study describing the epidemiology of Ebstein’s anomaly
in Europe and its association with maternal health and medication exposure during
pregnancy through population-based data, reported that cases exposed to maternal
mental health conditions/medications had an increased adjusted odds ratio risk of
2.64 compared with cardiac controls rather than lithium. The authors therefore
emphasize that changing or stopping medication to avoid foetal exposure in the rst
trimester may not be preventive for either the mother or the foetus.
10.2.3 Foetal andNeonatal Periods
Lithium use during the foetal period is likely to lead to a signicant increase in birth
weight (Diav-Citrin etal. 2014). In a recent systematic review including 28 studies—10 of which meeting the criteria for inclusion in a meta-analysis—and exploring 1402 newborn babies and 2595 women exposed to lithium, the review found
slightly increased adverse pregnancy outcomes for women taking lithium for both
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A.-L. Sutter-Dallay and F. Gressier
the rst trimester only and any time during pregnancy, while the meta-analysis
found increased odds for preterm birth, and a large size for gestational age with
lithium at any time during pregnancy (Callovini etal. 2024). In the retrospective
observational cohort study of Imaz etal. (2024), 56% of neonates presented transient acute complications with neonatal hypotonia being the most frequent outcome
(N=15).
Thus, paediatricians should carefully monitor babies during the rst 48h for
foetal goitre, hypotonia, bradycardia, arrhythmias, systolic murmur, hypothermia,
cyanosis, tachypnoea, and poor sucking reex (Newport etal. 2005), although most
of the reports described full recovery of the infants (Iqbal etal. 2001; Sutter-Dallay
etal. 2015). The recommendation is therefore to refer these patients to maternity
hospitals with day and night neonatal paediatric resources, in a collaborative network involving perinatal psychiatrists and trained obstetric teams (Belzeaux
etal. 2024).
10.2.4 Child Development
The question of an effect on foetal brain development in the long term remains, as
brain structures develop throughout pregnancy and may be particularly susceptible
to the impact of psychotropic drugs. To date, the extreme paucity of data does not
allow any conclusions. An animal study reported long-term effects with “anxious”
persistent behaviour in pups of dams treated (Youngs et al. 2006). Results at 5
(Schou etal. 1973) and 15years of age (Van Der Lugt etal. 2012) suggest no distinctive features of these babies as they mature. A more recent study (Forsberg etal.
2018) exploring a small clinical cohort showed no signicant association between
mothers’ prenatal exposure to lithium or mood disorders and offspring’s IQ.Finally,
the latest systematic review from Haskey and Galbally (2017) concluded that the
existing data on lithium are reassuring, but are of limited quality, indicating that
further research is still required.
10.2.5 Maternal Management
The increase in the distribution volume and in renal excretion rates among pregnant
women usually leads to an increase of doses during pregnancy, to maintain blood
levels as low as possible within the therapeutic range. Note that this recommendation is applicable to all psychotropic substances. A study providing the kinetic of
lithium blood levels during pregnancy, showed decrease in the rst trimester
(−24%), reached a nadir in the second trimester (−36%), increased in the third trimester (−21%) and were still slightly increased postpartum (+9%) (Wesseloo etal.
2017a). Given these variations, it is recommended to perform serum assays every
4weeks up to 36weeks of gestation, and then weekly until birth (NICE 2020). After
birth, the decline of distribution volume will lead to a decrease in doses because of
the risk of overdosage. Thereafter, requirements will be adapted according to
10 Mood Stabilizers inPregnancy
standard protocols, while maintaining special vigilance in the rst 15days postpartum. Note that some authors (Newport etal. 2005; NICE 2020) propose to achieve
a therapeutic window in 24–48ours before delivery when scheduled, or upon start
of delivery, with reintroduction immediately after birth.
267
10.3 What toDo
Lithium is no longer really contraindicated during the rst trimester of pregnancy
and is certainly not in itself an indication for termination of pregnancy today. The
risk of birth defects must also consider in light of the availability of ultrasound
screening and the progress in paediatric cardiac surgery. Here, even more than with
other psychotropic drugs, assessing the benet/risk ratio for each patient is essential. Viguera etal. (2000, 2007) have emphasized the importance of mood stabilization during pregnancy when necessary: women who stop their lithium treatment
during pregnancy have a risk of postnatal recurrence twice as high as non-pregnant
patients, and this recurrence may occur 4 times more rapidly and last 5 times longer.
If the choice is to stop treatment, discontinuation must be progressive, even if the
embryo is exposed, because the teratogenic risk is currently considered to be less
than that of decompensation generated by abrupt cessation (Burt and Rasgon 2004).
If treatment is continued throughout the pregnancy, the marked variation in blood
volume and the increased rate of renal excretion during pregnancy make regular
monitoring of maternal plasma and erythrocyte levels of lithium necessary.
Progressive decrease in dose in the days preceding birth is proposed by some authors
to avoid an overdose in the immediate postpartum period. In this perspective, proper
hydration must be maintained during labour to avoid neonatal overdosing. In the
postpartum, regular assays of plasma and erythrocyte lithium should be performed
and dosage adjusted until the appropriate balance is obtained.
To conclude and in line with the expert consensus paper of Fiorillo etal. (2023),
it is important to notice that there is “a discrepancy between evidence-based recommendations and clinical practice in using lithium treatment for patients with bipolar
disorder (…). It is necessary to reinvigorate the clinical and academic discussion
about the efcacy of lithium, to counteract the decreasing prescription trend of one
of the most effective drugs available in the whole medicine”.
10.4 Antiepileptic Drugs
With regard to knowledge on prenatal exposure to antiepileptic drugs, the main difculty remains that of the effects of the underlying pathology, since the vast majority of publications examine epileptic disorders and not their prescription in bipolar
disorders. A very recent systematic review and meta-analysis of the risks of adverse
pregnancy outcomes associated with antiseizure medications (ASMs) for any indication (Berry-Noronha etal. 2025) explored 16,941,373 pregnancies or live births
(14,437,221 pregnancies with maternal outcome data and 14,938,972 live births
268
with foetal/neonatal outcome data). Compared with pregnancies in unaffected
women, those exposed to ASMs had increased odds of several adverse outcomes
including preterm birth (OR 1.30, 95% CI 1.09–1.54), caesarean section (OR 1.43,
95% CI 1.13–1.81), gestational diabetes (OR 1.44, 95% CI 1.07–1.94), induction of
labour (OR 1.46, 95% CI 1.15–1.86), preeclampsia (OR 1.33, 95% CI 1.02–1.72),
spontaneous miscarriage (OR 1.42, 95% CI 1.01–2.01), and spontaneous fetal loss
(OR 2.54, 95% CI 1.04–6.24). Comparison of outcomes between untreated women
with the same ASMs indications and unaffected women showed that some differences (preterm birth, caesarean section, gestational diabetes, and preeclampsia)
were largely attributable to the underlying condition, particularly epilepsy. With
regard to the use of antiepileptic drugs for their mood-stabilizing indication, there
are virtually no data to draw any conclusions at present.
A.-L. Sutter-Dallay and F. Gressier
10.4.1 Placental Transfer
The work of Bank etal. (2017) found mean umbilical-to-maternal ratios for total
concentrations ranging from 0.79 for carbamazepine to 1.20 for valproic acid, and
mean umbilical-to-maternal ratios for free concentrations ranging from 0.86 for
valproic acid to 1.42 for carbamazepine, indicating complete placental passage.
However, in this study, neither umbilical cord concentrations nor umbilical-tomaternal ratios were associated with adverse neonatal outcomes.
10.4.2 Carbamazepine
10.4.2.1 Embryonic Period: Organogenesis
Data about the use of carbamazepine during pregnancy thus mainly concern women
with epilepsy and reports about women with psychiatric disorders are extremely
rare, although this antiepileptic drug is indicated for bipolar disorder. Either the
Food and Drug Administration (FDA) or the European Medicine Agency (EMA)
does not contraindicate it to date for use during pregnancy for epileptic patients, but
consider, as stipulated by the ANSM (Agence Nationale de Sécurité du Médicament
et des produits de santé) that carbamazepine is a teratogenic drug as the risk of malformation is up to 5.9%, which is 2–3 times higher than in the general population
(ANSM,
renforcement- de- linformation- des- femmes- pour- les- sensibiliser- aux- risquesencourus- par- les- enfants- a- naitre? 13/12/2024).
https://ansm.sante.fr/actualites/carbamazepine- et- grossesse-
10.4.2.2 Foetus Neonate andChild Development
Increased risks of small head circumference and low birth weight for gestational age
have been reported (Galbally etal. 2010; Veiby etal. 2014). The enzyme-inducing
effect of carbamazepine must also be considered in the neonatal care of the baby.
Most studies of its effect on child cognitive development report a slight impact,
specically on verbal abilities (Baker etal. 2015; Van Der Pol etal. 1991). More
10 Mood Stabilizers inPregnancy
269
recently, a cohort of 3,182,773 children, of which 17,495 were exposed to ASMs in
pregnancy issued from routinely collected primary care data from the UK and
nationwide Swedish registries, authors found that children exposed to carbamazepine were 1.25 times more likely to be diagnosed with autism (95% CI: 1.05–1.48)
and 1.30 times more likely to be diagnosed with intellectual disability (95% CI:
1.01–1.69) (Madley-Dowd etal. 2024).
10.4.2.3 What toDo
If the prescription of carbamazepine is unavoidable, the risk of congenital malformations necessitates supplementation with folic acid for 2months before and after
conception to prevent neural tube defects (Gedzelman etal. 2012). Ultrasound monitoring is recommended along with a possible assay of maternal serum levels of
alpha-fetoprotein before the 18th week of gestation (Galbally etal. 2010), underlying the absolute necessity for these women to be followed by obstetric and paediatric teams that are trained and able to manage complications. Lastly, regular care and
monitoring in a neonatal paediatric department is recommended for the child.
10.4.3 Valproates
10.4.3.1 Embryonic Period: Organogenesis
The prescription of valproates is contraindicated during the rst trimester of pregnancy. The teratogenic risk is signicant, with a global malformation rate around
10% (four times higher than with other antiepileptic drugs), mainly of the central
nervous system (1–2% compared to 0.1% in the general population) (Ernst and
Goldberg 2002; Galbally etal. 2010; Hernández-Díaz etal. 2012). In cases of exposure in early pregnancy, some authors consider that the risk of teratogenesis outweighs that of mood decompensation and advocate rapid cessation. Specic
ultrasound to screen for malformations is required as early as possible, and abortion
counselling must be offered if they are suspected.
10.4.3.2 Fetus andNeonate
Valproate may lead to a haemorrhagic syndrome in the newborn, although its cause
is still unclear (possibly a combination of impaired platelet aggregation, thrombocytopenia, and decreased brinogen). Monitoring of haemostasis is thus required in
the mother before delivery and in the neonate at birth. The baby also appears to be
at risk of hepatocellular insufciency. Some studies have described a risk of neonatal hypoglycaemia (Galbally etal. 2010). Another important concern is the risk of
impaired cognitive development in infants of mothers treated with valproates
(Eriksson et al. 2005; Haskey and Galbally 2017). The EMA issued a warning
against prescribing these drugs to women and girls of childbearing age (http://www.
ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Valproate_
and_related_substances/human_referral_prac_000032.jsp&mid=WC0b01ac0580
5c516f). The French national agency of medications banned the prescription of val-
proates in women of childbearing age (Casassus 2017).
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A.-L. Sutter-Dallay and F. Gressier
Recently, Madley-Dowd et al. (2024)—previously mentioned—showed that
children exposed to valproate were more likely to receive a diagnosis of autism,
intellectual disability, and ADHD, when compared to children not exposed to ASMs.
10.4.3.3 What toDo
In view of the clear increase in the risk of congenital malformations and developmental disorders caused using valproates during pregnancy, switching to a different
molecule before pregnancy—or as soon as pregnancy is discovered—is the rst-line
recommendation. In case of antenatal exposure, supplementation with folic acid
from 2months before to 2months after conception is essential to help to the prevention of neural tube defects (Gedzelman etal. 2012).
Monitoring by special ultrasonography is strongly recommended, together with
a possible assay of maternal serum levels of alpha-fetoprotein before the 18th week
of gestation. During pregnancy and after childbirth, maternal and child coagulation
and hepatic functions and maternal blood concentrations of valproate should all be
monitored regularly.
Note that the prescription of valproates is now contraindicated in women of
childbearing age unless alternative treatments are ineffective or not tolerated (WHO
2023, https://www.who.int/news/
item/02- 05- 2023- use- of- valproic- acid- in- women- and- girls- of- childbearingpotential).
10.4.4 Lamotrigine
10.4.4.1 Embryonic Period: Organogenesis
The recent systematic review and network meta-analysis of congenital malformations and prenatal outcomes (Wang et al. 2025) exploring 3,042,997 showed that
pregnant women taking lamotrigine did not show signicant differences compared
with the unexposed group in terms of congenital malformations (OR, 1.21; 95% CrI
0.86–1.64). However, some studies suggested a possible dose-effect relation with
cleft palate, not conrmed to date (Campbell etal. 2014; Vajda et al. 2025). On the
other hand, analysis of 490 pregnancies treated with lamotrigine monotherapy and
214 pregnancies in women with epilepsy who were not exposed to antiepileptic
drugs during at least the rst half of pregnancy showed that there was a foetal malformation rate of 4.49% in the LTG-exposed pregnancies and 3.27% in the untreated
group (risk ratio=1.37; 95% C.I. 0.60, 3.16). Logistic regression provided no evidence that the lamotrigine-associated risk of malformations was related to lamotrigine dose, although the body regions affected by malformations tended to differ
between lamotrigine-treated and untreated pregnancies. Nevertheless, the authors
emphasize that if the foetal malformation rates of lamotrigine monotherapy are used
as a comparator to assess the risk of foetal malformation associated with other antiepileptic drugs, the results may suggest falsely reassuring results.
10 Mood Stabilizers inPregnancy
271
10.4.4.2 Fetus andNeonate
In 2018, a review concluded that “it is not clear that fetuses of lamotrigine-exposed
pregnant women are at higher risk of malformation or neurodevelopmental delay”
(Kong etal. 2018). A recent review and meta-analysis on neurodevelopmental outcomes after prenatal exposure to lamotrigine monotherapy in women with epilepsy
found that lamotrigine monotherapy is not statistically associated with neurodevelopmental disorders as a whole, language disorders or delay, diagnosis or risk of
ASD and diagnosis or risk of ADHD. However, the meta-analyses found an
increased risk of psychomotor developmental disorders or delay and cognitive
developmental delay in less than 3years old children. Finally, the authors underline
that these ndings were exclusively based on possible biased observational studies
of a limited number of children (Peron etal. 2024).
10.4.4.3 What toDo
Lamotrigine was found as not being inferior to lithium in the prevention of severe
postpartum episodes, suggesting that lamotrigine could be a reasonable alternative
treatment option for bipolar disorder during pregnancy in patients with vulnerability
for depression and may prevent severe episodes postpartum (Wesseloo etal. 2017b).
In view of the persistent doubts about the safety of antenatal exposure in terms of
teratogenesis, prescribers must always bear in mind the rule of seeking the minimum effective dose. In this context, blood tests can guide decisions.
10.5 Conclusion
Table 10.1 summarizes key points.
One of the most important features of the perinatal period is the real possibility
of preventive care to protect the health of both mother and child. Psychiatrists must
always be aware of the importance of discussing pregnancy plans with women of
childbearing age with bipolar disorder, preferably before they become pregnant.
If pregnancy occurs, regular follow-up by a specialist team should be offered
whenever possible. Management needs to be embedded in a multidisciplinary network to anticipate specic postnatal care, such as prolongation of maternity stay,
home help, community-based interventions or any other type of specic care foreseen by local or national perinatal mental health policies. Given the complexity of
the treatment, the psychiatrist must ensure close interdisciplinary care, if possible in
the form of a liaison and consultation service; it is particularly important that all
involved are aware of the effects of medication on the mother, the embryo and the
foetus, including the effects that vary according to gestational age.